The administration of drugs percutaneously or transdermally has a number of advantages and is favoured in the case where drugs are not effectively administered by the oral route but where systemic administration is required. This is especially true for drugs which are subject to a first-pass hepatic metabolism or which are susceptible to deactivation by digestive enzymes.
There are also a number of problems associated with the administration of drugs by the transdermal route, for example, a rate of uptake of drug which is therapeutically effective may not be achievable. The use of penetration enhancers, for example, dimethylsulphoxide, N,N-dimethylformamide and others is employed to promote uptake. However, such penetration enhancers are not always effective or sufficient to achieve adequate percutaneous absorption.
Also the manufacture of stable transdermal devices can be a problem because it may not be possible to find a carrier medium which can maintain the drug in a stable condition until use and from which the drug can be successfully transported to and into the skin following application of the transdermal device at the site of administration.
For some drugs such as glyceryl trinitrate fluctuations in blood level rather than a continuous constant level is required. Thus there is a need for devices or systems capable of periodic or pulsed drug delivery.
For drugs that are not amenable to passive administration by the percutaneous route or for drugs that are effectively percutaneously absorbed as charged molecules, iontophoretic drug delivery is gaining increasing popularity.
However, iontophoretic drug delivery also has a number of problems, not least of which is the trauma caused by burns and pain which may be associated with the use of this type of delivery which involves migration of drug molecules in the skin under the influence of an electric field. Hence conventional iontophoresis as a means of drug delivery may not achieve good patient compliance.
One solution for dealing with the problems associated with iontophoresis is the electrode device of U.S. Pat. No. 4,722,726, one of the stated objects of which is to provide an iontophoretic drug delivery device that inhibits the current carrying capacity of ions in the carrier medium that compete with the active ingredient and lead to progressive diminution of effective drug transfer during the iontophoretic delivery thereof.
U.S. Pat. No. 4,731,049 discloses a cell for electrically controlled transdermal drug delivery by iontophoresis. The drug is bound on an ion exchange resin or medium or an immobilized ligand affinity medium located in the drug reservoir. Drug delivery occurs upon the application of an electrical current of generally small proportions to the reservoir or to an adjacent ion reservoir separated from the drug reservoir by a semi-permeable membrane.
It is an object of the present invention to provide a device and method for the delivery of drugs by the percutaneous route which obviates the trauma in the form of burns and discomfort experienced by the patient and yet achieves an uptake and control of drug by skin which is enhanced when compared to conventional passive delivery.
Investigations carried out by us have shown that by using an electric circuit within a device to actively transport drug from a drug reservoir forming part of said device, but wherein the skin does not form part of the circuitry of the device in contradistinction to an iontophoretic device, one achieves drug delivery rates greater than those achieved with conventional passive delivery.